Medicine and Pharmacology

Abstract: Major depressive disorder remains a leading cause of disability, and decades of monoam-ine-centered pharmacology have yielded delayed and often incomplete relief. Rapid-acting antidepressants reshaped the field by linking swift symptom improvement to glu-tamatergic plasticity, yet durable benefit depends on how newly reconfigured circuits are stabilized and tuned. This review synthesizes evidence that antidepressant efficacy arises from the coordinated engagement of synaptic plasticity, spanning induction and consoli-dation, and intrinsic excitability, which provides gain control, and proposes an integrated framework to guide future discovery. It first outlines induction through N-methyl-D-aspartate receptors (NMDARs) and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPARs), exemplified by ketamine and esketamine, followed by consoli-dation mediated by tropomyosin receptor kinase B (TrkB) signaling, translational disinhi-bition via eukaryotic elongation factor 2 kinase (eEF2K), and presynaptic stabilization in-dexed by synaptic vesicle glycoprotein 2A (SV2A); together, these processes transform transient potentiation into persistent network change. It then highlights intrinsic excitabil-ity, emphasizing voltage-gated potassium channel subfamily Q (Kv7), hyperpolarization-activated cyclic nucleotide-gated (HCN), and G protein-gated inwardly rectifying potassi-um (GIRK) channels as circuit-level governors that normalize firing and limit relapse-prone hyperexcitability. Finally, it presents a phase-aware Induction–Consolidation–Maintenance (ICM) roadmap, supported by SV2A positron emission tomography (PET) and electroencephalography (EEG)/functional magnetic resonance imaging (fMRI) bi-omarkers, to personalize treatment timing and combinations. This dual-target strategy re-frames antidepressants as network reprogrammers and suggests broader relevance for circuit repair across neurology and psychiatry.

Abstract: This systematic review of 25 original studies examined the efficacy of density gradient centrifugation (DGC) combined with magnetic-activated cell sorting using Annexin V (MACS) for improving sperm quality in infertile men undergoing ICSI. The evidence consistently demonstrates that DGC-MACS significantly reduces sperm DNA fragmentation, with reported reductions ranging from 2.82% to 21.9% in absolute terms, and relative reductions of 39%-83%. The combination of DGC followed MACS achieved superior outcomes compared to either technique alone, reducing DNA fragmentation index (DFI) 4.1 to ± 1.3% compared with 8.1 ± 4.1% for DGC alone and 7.4 ± 3.9% for MACS alone. The treatment improved sperm motility, membrane integrity and overall spermatozoa health by reducing protamine deficiency and chromosomal abnormalities. Clinical results in ICSI cycles showed that although fertilization rates were similar between the treated and control groups, DGC followed by subsequent MACS treatment significantly improved embryo quality (72.5% vs. 51.47% top-quality day-3 embryos), blastocyst formation rate (69.69% vs. 48%), pregnancy rates (60.7% vs. 51.5%, p=0.014), and live birth rates (47.4% vs. 31.2%, p=0.001) with a reduced miscarriage rate (14.7% vs. 20.6%, p=0.034). The technique proved most beneficial in patients with high baseline DNA fragmentation (≥30%) and in those with asthenozoospermia or asthenoteratozoospermia. Studies suggest, and consistently supported by our study results, that performing DGC before MACS (DGC-MACS) may yield superior results compared to the reverse sequence. This is because DGC leads to a primary separation of sperm based on density, motility, and morphology and thus producing a high-density fractions enriched in morphologically normal sperms. MACS by specifically binding to phosphatidylserine (PS) residues on sperm membranes selectively removes PS‑positive/apoptotic sperm in a subsequent purification step. Overall, the literature strongly supports the use of combined DGC-MACS as an effective sperm preparation technique for ICSI in infertile men with elevated sperm DNA fragmentation.

Abstract: Early-onset colorectal cancer (EOCRC), defined as colorectal cancer diagnosed before the age of 50 years, has become an emerging global health concern due to its steadily increasing incidence. Compared with late-onset colorectal cancer, EOCRC often presents with more advanced disease and exhibits distinct clinical and biological characteristics. Notably, younger patients are more likely to present with synchronous metastases and multi-organ dissemination at the time of diagnosis. This mini-review summarises current evidence regarding metastatic patterns and the biological mechanisms underlying multi-organ metastasis in EOCRC. The liver remains the most common metastatic site in EOCRC, primarily due to portal venous drainage from the colorectal region. However, studies suggest that EOCRC patients have a higher likelihood of additional metastatic involvement of the lungs, peritoneum, and distant lymph nodes, with occasional spread to the bone and brain. Several biological mechanisms may contribute to this aggressive metastatic behaviour. Distinct molecular alterations, including KRAS and BRAF mutations and microsatellite instability, have been reported in EOCRC and may influence tumour progression and metastatic potential. In addition, tumour microenvironmental changes such as epithelial–mesenchymal transition and angiogenesis play critical roles in facilitating tumour invasion, intravasation, and colonisation of distant organs. Hereditary predisposition, lifestyle-related risk factors, and gut microbiome alterations have also been implicated in EOCRC pathogenesis. A clearer understanding of the metastatic cascade and its molecular drivers in EOCRC is essential for improving early detection and developing targeted therapeutic strategies. Future research integrating molecular profiling and clinical outcomes may help optimize personalised treatment approaches and improve prognosis in this increasingly recognised patient population.

Abstract: Cancers are thought to result from the interaction of a small set of mutations in genes that regulate cell growth. A sixty-five year series of incidence data is available for cancer of the pancreas, spanning the period over which incidence increased threefold. These data were analysed using a multi-hit mutation model. The analysis yielded as parameters the averages of the number of interacting genes (with the number four being within the range found), the rate of their mutation, the age at which mutations began to accumulate and the number of persons at risk. Only this last parameter showed a significant increase over the years, a period which coincided with increased consumption of sugars. The effect of glucose on the proliferation of cells of the pancreas is suggested as a basis for these findings.

Abstract: Background/Objectives: Acute pancreatitis (AP) is a heterogeneous disease with outcomes ranging from mild to severe. Early risk stratification is essential, but commonly used scoring systems are often complex for routine use. This study aimed to evaluate the predictive value of systemic inflammatory indices derived from complete blood count parameters in assessing disease severity in AP. Methods: This retrospective study included 454 patients with AP. Demographic, clinical, and laboratory data were obtained from electronic medical records. Systemic inflammatory indices (NLR, PLR, MLR, dNLR, SII, SIRI, and AISI) were calculated from admission laboratory values, with logarithmic transformation applied to selected indices. Disease severity was classified according to the Revised Atlanta Classification, and patients were grouped as mild or moderate-to-severe. Statistical analyses included ROC curve analysis and logistic regression. Results: Among 454 patients, 371 (81.7%) had mild and 83 (18.3%) had moderate-to-severe AP. Patients with more severe disease were older and showed significant differences in several laboratory parameters. NLR, PLR, SII, dNLR, and Log-SII were significantly higher in the moderate-to-severe group. However, all indices demonstrated limited discriminative performance, with dNLR showing the highest AUC (0.612). In multivariate analysis, only age and C-reactive protein (CRP) remained independent predictors of disease severity. Conclusions: Systemic inflammatory indices are associated with disease severity in AP; however, their predictive performance is limited. Conventional parameters such as age and CRP remain more reliable for risk stratification.

Abstract: Background/Objectives: Fibrodysplasia ossificans progressiva (FOP) is an ultra rare genetic disorder causing progressive heterotopic ossification. The dental phenotype has never been systematically characterised. We quantified dental pathologies and oral health related quality of life across three age groups of genetically confirmed FOP patients and compared them with 156 matched healthy controls (2022–2025). Methods: 52 FOP patients (Group I: 1–5 y, n=14; Group II: 6–17 y, n=21; Group III: 18–35 y, n=17) underwent standardised dental examination (Decayed, Missing, and Filled Teeth index (DMFT), Oral Hygiene Index Simplified (OHI S), Angle classification, temporomandibular joint (TMJ) assessment), computed tomography (CT) densitometry, sialometry, salivary crystal analysis, and Oral Health Impact Profile 14 (OHIP 14). Statistical analysis used Kruskal Wallis, Mann Whitney U, Benjamini Hochberg false discovery rate (FDR) correction, and effect sizes. Results: Caries (DMFT≥4) was highly prevalent across all FOP groups (82–86%) and significantly higher than in controls (84.6% vs. 38.5%, p<0.001). Chronic stomatitis increased steeply with age (7.1% in Group I → 100% in Group III, p<0.001); it was universal in FOP adults vs. 6.4% in controls. Enamel hypoplasia (21.4% → 58.8%) and Angle class II malocclusion (0% → 47.1%) also showed large age group differences. Total TMJ disorders were observed in 7.1% of Group I and 100% of Group III (p<0.001); maximal mouth opening was lower by 17.4 mm in Group III (Cohen’s d=2.1). Salivary flow rate was 20% lower in adults (0.35→0.28 ml/min, p=0.01). Calcium phosphate crystals were detected in 17.6% of adults and correlated with CT calcification grade (ρ=0.67, p=0.003). OHIP 14 total score was higher (worse) in Group III (48.9 vs. 12.4 in Group I, Cohen’s d=1.95). Conclusions: This first systematic characterisation of the dental phenotype in FOP shows that chronic stomatitis and TMJ dysfunction become nearly universal by early adulthood, severely impairing quality of life. The correlation between salivary calcium phosphate crystals and CT calcification generates the hypothesis of a non invasive biomarker, requiring prospective validation. The proposed clinical phenotype and minimally invasive recommendations provide a framework for safer dental management of FOP patients.

Abstract: Implant-supported overdentures improve denture retention and patient satisfaction, but debonding of attachment housings from the denture base remains a frequent prosthetic complication. This in vitro study evaluated the influence of attachment housing and denture base materials on debonding occurrence and maximum tensile force in resin-cemented attachment housing–denture base complexes subjected to cyclic mechanical loading. Thirty standardized specimens were digitally designed and fabricated from 3 denture base materials—polymethylmethacrylate (PMMA), polyetheretherketone (PEEK), and cobalt-chromium (Co-Cr)—and combined with either titanium or PEEK attachment housings, which were bonded with a dual-polymerized resin cement. Specimens were subjected to 1,100 cycles of alternating tensile and compressive loading, and debonding occurrence and maximum tensile force were recorded. Debonding occurred in 60% of specimens and differed significantly among denture base materials, with no debonding observed in Co-Cr specimens, whereas debonding occurred in 75% of PMMA and PEEK specimens. Co-Cr specimens also demonstrated significantly higher maximum tensile force values than PMMA and PEEK groups, while attachment housing material showed no significant effect. Within the limitations of this in vitro study, the denture base material significantly influenced debonding and tensile force during cyclic loading, whereas the attachment housing material did not demonstrate a significant main effect.

Abstract: Streptococcus pyogenes and Streptococcus agalactiae are major Gram-positive patho-gens implicated in recurrent and invasive genital infections, and the rise of antimicrobial resistance underscores the need for alternative localized therapies. This study combined molecular docking with a prospective pilot clinical evaluation of an essential-oil-based vaginal capsule formulation intended for localized intravaginal administration. Terpinen-4-ol, isoflavone, and secoisolariciresinol diglucoside (SDG) were analyzed against two bacterial targets - the redox-sensing transcriptional repressor Rex from S. agalactiae and the protein tyrosine phosphatase from S. pyogenes - using the 1-Click Docking platform and the Lamarckian Genetic Algorithm. In parallel, 47 women aged 19-27 years were identified with vaginal and/or cervical colonization or infection caused by S. agalactiae or S. pyogenes, and 34 of them entered a prospective pilot treatment study with once-daily vaginal capsules for 7 days; persistent positive cases received an additional 7-day course. Isoflavone and SDG showed the most favorable interactions against the S. agalactiae target, while SDG also displayed comparatively favorable interaction against the S. pyogenes target. In the clinical pilot cohort, microbiological eradication after completion of therapy reached 91.7% for S. agalactiae and 80.0% for S. pyogenes. The parallel trend between stronger in silico prioritization for the S. agalactiae-directed target and higher clinical eradication in the pilot cohort supports a cautious translational hypothesis, but the absence of a control group, the limited sample size, and the exploratory nature of the clinical dataset require restrained interpretation. Overall, these findings support further controlled studies designed to test whether the computationally prioritized phytocompounds contribute to measurable in vivo benefit within localized antimicrobial strategies.

Abstract: Background: Although Diagnostic Reference Levels (DRLs) based on anatomical regions are widely used in Computed Tomography (CT) imaging, a clinical-indication-based approach provides a more accurate representation of daily practice and protocol variation. This study aimed to establish typical radiation doses for common CT clinical indications among adult patients at King Abdulaziz University Hospital (KAUH) in Saudi Arabia. Methods: This retrospective cross-sectional study included 298 adult patients who underwent CT examinations between 2020 and 2025 using two dual-source scanners operating in single- and dual-source modes. Demographic data, acquisition parameters, and radiation dose metrics, including volume CT dose index (CTDIvol) and the dose–length product (DLP) were extracted from scanner consoles. Six clinical indications were analyzed: brain trauma, sinusitis, chest metastases (chest Mets), interstitial lung disease (ILD), abdominopelvic metastases (AbdPel Mets), and hernia. Results: Typical median CTDIvol values in mGy were 36.4 for brain trauma, 3.4 for sinusitis, 4.9 for chest Mets, 5.6 for ILD, 7.2 for AbdPel Mets and hernia. Corresponding DLP values in mGy·cm were 654, 50, 173, 188, 344, and 369, respectively. Brain trauma demonstrated the highest radiation exposure, whereas sinusitis CT showed the lowest. Most values were comparable to or lower than international DRLs. Conclusions: This study provides the first comprehensive clinical-indication-based DRL data in Saudi Arabia beyond anatomical benchmarks, supporting ongoing dose optimization and future national DRL development.

Abstract: Background/Objectives: Chorioamnionitis, an inflammation, with or without infection, involving the amniotic fluid, placenta, fetal membranes or decidua, can significantly impact fetal and neonatal development. This study aimed to determine the incidence of chorioamnionitis and confirm its correlation with neonatal morbidity and mortality, in a single tertiary center. Materials and Methods: This observational, retrospective study was conducted over three years (2019-2021) in a tertiary neonatal intensive care unit, examining 80 preterm infants born at 23-28 weeks of gestation. Pearson correlation and χ² tests were used to assess associations between chorioamnionitis exposure and neonatal outcomes. Results: Among the 80 newborns analysed, clinical chorioamnionitis was identified in 12 preterm infants, while 46 presented histological chorioamnionitis. A weak but significant negative correlation (r = –0.27, p = 0.0152) between gestational age and chorioamnionitis stage indicated that preterm infants born at lower gestational ages are more frequently exposed to this intrauterine infection. Histological chorioamnionitis stage was significantly associated with early onset sepsis (r=0.31, p=0.0048), severity of respiratory distress syndrome (r=0.25, p=0.0242), bronchopulmonary dysplasia (r=0.26, p=0.0212), and retinopathy of prematurity (r=0.26, p=0.0249). Conclusion: Histological chorioamnionitis was significantly associated with early onset sepsis, respiratory distress syndrome, bronchopulmonary dysplasia, and retinopathy of prematurity. No significant association was found between chorioamnionitis and neonatal mortality. While clinical diagnostic criteria for chorioamnionitis demonstrated good specificity, their poor sensitivity underscores the urgent need for improved diagnostic tools.

Abstract: Background: Dengue virus (DENV), chikungunya virus (CHIKV), and Zika virus (ZIKV) co-circulate across the Americas and share Aedes mosquito vectors, creating conditions for concurrent infections. Whether coinfection increases clinical severity remains uncertain because clinical syndromes overlap, diagnostic windows are short, and flavivirus serology is prone to cross-reactivity. Objective: To synthesize evidence on the association between DENV, CHIKV, and ZIKV coinfection and clinical severity in the Americas. Methods: An integrative review was structured according to the framework proposed by Whittemore and Knafl. PubMed/MEDLINE, Scopus, Web of Science, LILACS, and SciELO were searched for publications from 2015 to 2026. Eligible studies involved human populations in the Americas and laboratory-confirmed dual or triple infection. Evidence was narratively synthesized by epidemiology, clinical severity, laboratory phenotype, neurologic or perinatal outcomes, diagnostic validity, and methodological quality. Results: Coinfection was repeatedly documented in settings of intense arboviral co-circulation, particularly when multiplex molecular assays were used. Evidence does not support a uniform increase in hemodynamic severity or mortality in all coinfected patients. Instead, DENV-CHIKV coinfection appears to produce a mixed phenotype combining dengue-like hematologic abnormalities with chikungunya-like arthralgia, whereas DENV-ZIKV interactions raise greater concern for diagnostic misclassification and immune-mediated neurologic or congenital outcomes. Conclusions: Arboviral coinfection in the Americas is better understood as a context-dependent interaction shaped by vector ecology, timing of infection, host immune history, and diagnostic method than as a simple additive syndrome. Prospective multicenter studies using standardized severity definitions and multiplex molecular confirmation are needed.

Abstract: Head and neck lymphedema (HNL) is a common complication of head and neck cancer (HNC) treatment, with upwards of 70-90% of patients suffering from this condition. Surgery and radiation, the backbones of HNC treatment, disrupt lymphatic networks through direct injury and fibrosis, leading to accumulation of lymphatic fluid in interstitial spaces. This causes swelling of external and internal structures, leading to decreased quality of life, cosmetic distress, social withdrawal, and functional deficits such as dys-phagia, dysphonia, and reduced cervical mobility. Having a reliable assessment tool is key to diagnosing and monitoring HNL; however, few tools specific to HNL exist. Cur-rently, the cornerstone of HNL treatment is conservative management with complete decongestive therapy, which shows mixed efficacy. There is a lack of surgical options as well as prophylactic interventions. Imaging of lymphatic channels is a promising mo-dality that can help providers guide and plan personalized therapies. This paper provides a narrative review of the pathophysiology, assessment, and prevention of HNL, high-lighting future directions for improvement.

Abstract: The mandibular cortical index (MCI) is a valuable screening tool for osteoporosis on dental panoramic radiographs; however, inter-examiner variability remains a significant challenge. This study aimed to evaluate the diagnostic performance and reproducibility of a closed-type generative AI (NotebookLM, Google) compared with eight dentists of varying experience levels. One hundred radiographs were evaluated in two sessions with an interval of at least two weeks. The intra-examiner reliability for the AI was exceptionally high (κ = 0.987), and its processing speed was approximately six times faster than that of the dentists. However, the agreement between the AI and the dentists remained at "slight agreement" or lower (κ < 0.2), statistically rejecting the null hypothesis of diagnostic equivalence. Notably, a "two-level discrepancy" was observed, where the AI interchanged Class 1 (normal) and Class 3 (severe) in over 10% of cases. In contrast, dentists demonstrated a significant learning effect, with inter-examiner agreement improving between sessions. These results suggest that while generative AI offers superior speed and reproducibility, its current decision-making logic deviates fundamentally from human expert criteria. Future integration should focus on hybrid models where AI serves as a standardized feedback tool while dentists provide final confirmatory diagnoses.

Abstract: Renal cell carcinoma encompasses a heterogeneous group of kidney tumors with wide variations in biological behavior, histologic subtype, and clinical aggressiveness. Accurate preoperative characterization is essential for management; however, it remains challenging due to overlapping imaging features and tumor complexity. CT is the most widely used imaging technique for renal mass evaluation, providing broad availability, high spatial resolution, and multiphasic acquisition capabilities. However, its ability to distinguish histologic subtypes and predict tumor aggressiveness remains limited. This review provides an updated overview of renal cell carcinoma epidemiology and evidence supporting CT as an essential imaging modality. It outlines key radiologic features of main histologic subtypes, highlights markers of aggressive behavior, and discusses the relationship between CT findings and the International Society of Urological Pathology (ISUP) grading system. We explore radiomics, summarizing its methodological foundations and applications in characterizing solid renal masses, emphasizing the need for multicenter studies and standardized radiomic workflows to develop accurate, reproducible tools for improving diagnostic accuracy and risk stratification for renal cell carcinoma.

Abstract: Parkinson’s disease (PD) encompasses marked heterogeneity across motor, cognitive, and non-motor domains, reflecting variable balances of neurodegeneration and compensation across distributed brain circuits. Diffusion MRI tractography enables pathway-specific characterization of white matter alterations and offers a framework for linking clinical subtypes to patterns of degeneration and compensation along individual tracts that are often obscured by skeleton-based or connectomic averaging. Although several tract-specific correlational diffusion studies have linked individual pathways to clinical features and progression, much of the literature has relied on group-level skeleton or network representations, limiting generalizability and reproducibility across subtypes. Here, we synthesize tractography-based evidence across PD subtypes—including tremor-dominant, postural instability/gait difficulty, freezing of gait, and cognitive phenotypes—while situating these findings within a complementary multimodal imaging context. We review diffusion models ranging from diffusion tensor imaging to advanced free-water, neurite and fixel-based frameworks, highlighting how these approaches constrain and interpret tract-level findings and help distinguish degenerative processes from adaptive neuroplasticity. Emerging analytical approaches, including harmonization pipelines, radiomic tractometry (the extraction of along-tract microstructural and radiomic features), and machine learning classifiers, further enhance tract-level sensitivity and reproducibility. Cognitive subtypes illustrate how degeneration of posterior association and limbic tracts, in interaction with non-dopaminergic systems such as cholinergic and noradrenergic pathways, shapes clinical progression. Integrating tractography with molecular, genetic, and functional markers enables subtype-specific biomarkers for risk stratification, prognosis, and targeted therapeutic intervention. We propose a conceptual and methodological roadmap for leveraging tractography to refine PD subtype definitions and inform precision neuromodulation and rehabilitation strategies.

Abstract: Introduction: A major health issue in individuals living at high altitude regions is an increase in the number of red blood cells (RBCs). This condition generates a series of physiological alterations, including the nervous system, where damage can occur due to increased blood viscosity. This increased viscosity, in turn, could compromise oxygen uptake, potentially leading to a degree of cognitive impairment. Objective: To determine the association between exposure to chronic hypoxia and sleep quality with the degree of cognitive impairment (IQ) in a young adult population residing at different altitude levels. Methodology: Two hundred apparently healthy subjects of both sexes, aged 21 to 26 years, permanently residing in four cities at different altitudes—Lima, Arequipa, Puno, and La Rinconada (50 participants per location)—were evaluated. Physiological variables such as oxygen saturation (SpO2), blood pressure (BP), heart rate (HR), and hemoglobin (Hb) and hematocrit (Hct) levels were measured. Cognitive impairment was assessed using the Montreal Cognitive Assessment (MoCA), and sleep quality was assessed using the Pittsburgh Sleep Quality Index (PSQI). ANOVA, chi-square, and linear regression models were used to analyze correlations. Results: Hemoglobin (Hb) levels increased gradually with altitude, reaching a maximum of 19.47 ± 3.01 g/dL in La Rinconada, while SpO2 decreased to 81.64% at the same site. Moderate to severe cognitive impairment was a finding exclusive to the La Rinconada population (5100 m), where only 10% of subjects remained unaffected. Regression analysis showed that for each unit increase in Hb, the MoCA score decreased by 0.59 points, indicating that elevated Hb levels were associated with varying degrees of cognitive impairment. No association was found between sleep quality and the degree of cognitive impairment. Conclusions: Chronic exposure to severe hypoxia (>5000 m) is associated with a greater presence of cognitive impairment, while sleep quality is not associated with any degree of cognitive impairment.

Abstract: Prolonged contact between oral mucosa and dental amalgam restorations may influence local epithelial homeostasis, although the immunohistochemical profile of clinically non-dysplastic mucosa exposed to long-term restorative materials remains insufficiently defined. This study investigated histopathological remodeling and the expression patterns of cytokeratin 19 (CK19), Ki67, and p53 in oral mucosal specimens adjacent to long-standing amalgam restorations. A total of 108 specimens were retrospectively analyzed, including 78 samples from mucosa in direct contact with amalgam restorations and 30 control specimens without amalgam exposure. Exposed cases were categorized according to contact duration: 5–10 years, 11–20 years, and ≥21 years. Epithelial and stromal changes were semi-quantitatively assessed, and immunohistochemical staining was evaluated using predefined scoring criteria. An exploratory Integrated Epithelial Remodeling Score (IERS), combining basal hyperplasia, inflammatory infiltrate, CK19 distribution, and Ki67 proliferative index, was used to estimate cumulative remodeling intensity. Longer amalgam exposure was significantly associated with increased inflammatory infiltrate, basal epithelial expansion, suprabasal CK19 expression, and higher Ki67 labeling indices (all p &lt; 0.001). CK19 redistribution showed positive associations with both inflammatory intensity and epithelial proliferative activity. IERS values differed significantly among exposure groups (p &lt; 0.001), with more pronounced remodeling in intermediate- and long-duration exposure categories. p53 expression showed statistically detectable but heterogeneous variation. No epithelial dysplasia was observed. These findings suggest that long-term contact with dental amalgam restorations is associated with a coordinated, non-dysplastic remodeling phenotype of the oral mucosa, characterized by inflammatory activation, CK19 redistribution, and reactive proliferative reinforcement. In this context, suprabasal CK19 expression may reflect adaptive epithelial plasticity rather than preneoplastic transformation.

Abstract: The use of technology-enhanced training for prehospital mass-casualty incident (MCI) preparedness has grown quickly, but there has been no comprehensive overview of how these technologies operate throughout the training process or how competencies are evaluated. This scoping review, conducted as part of the MCIPHER (Mass-Casualty Incident Prehospital Emergency Response) project, followed the Arksey and O'Malley framework and PRISMA-ScR guidelines. We searched seven databases and additional sources, screened 2,105 records, and included 28 studies published from 2015 to 2025. Virtual reality was the most common method (43%), followed by hybrid approaches (29%) and screen-based simulations (21%). We identified five key analytical constructs. Three were derived from the data: the Technology Function Spectrum revealed that half of the studies used dual-purpose platforms for both training and performance assessment; the Data Capture Architecture linked embedded data collection to advanced learning outcomes (L2+); and the Pedagogical Transparency Gap showed that 75% of studies did not specify a training design framework. Two other constructs — the Immersion-Evaluation Paradox and the Scalability-Rigor Tension — suggest areas for future research. Using a modified Kirkpatrick framework with an L2+ (Applied Learning) sub-level, 56% of completed studies demonstrated applied learning through embedded performance assessments. Overall, these findings suggest that investments in MCI preparedness should focus more on measurement capabilities than immersion, incorporate assessment into training platforms, and work to reduce geographic and resource disparities.

Abstract: Cranial cruciate ligament (CrCL) rupture in cats is less common than in dogs, and its optimal treatment remains a subject of debate. The aim of this study was to evaluate the application of cranial tibial wedge osteotomy technique (CTWO) as a dynamic stabilization technique in cats with CrCL rupture, describing the technical aspects and clinical outcomes obtained. Five cases with a confirmed diagnosis of CrCL rupture between 2020 and 2024 were included in this study. All patients were treated with CTWO using specific osteosynthesis locking plates for this technique in dogs and a complementary cerclage wire. Radiographic rechecks were performed at 8 and 12 weeks postoperatively and clinical evaluations were performed 24 hours, 8 weeks, 12 weeks and six months postoperatively in every patient. Successful and complete bone healing of the tibial osteotomy was observed in every case. No intraoperative or postoperative complications related to implants or soft tissues were recorded. All cats achieved a complete functional recovery without lameness at the last recheck six months after surgery. The technique was performed without significant technical difficulties, providing adequate stability and favorable clinical outcomes in all cases. Although the use of a cranial tibial wedge osteotomy in combination with a tibial plateau leveling osteotomy (TPLO) was reported by Hoot et al to treat a cruciate ligament rupture in a cat presenting a deformity of the proximal tibia (Hoot et al), to the authors´ knowledge the use of the cranial tibial wedge osteotomy as single technique to treat the CrCL rupture in cats has not been previously reported in the literature. These preliminary results support the use of CTWO as an effective surgical alternative for the treatment of CrCL rupture in cats. However, further studies with a larger number of cases and a longer follow-up are required to evaluate better its clinical application, outcomes and influence on osteoarthritis progression in the long term.

Abstract: Cardiogenic shock secondary to acute myocardial infarction complicated by mechanical failure remains associated with high mortality despite advances in cardiac surgery and mechanical circulatory support. We report the case of a 42-year-old patient with poste-rior papillary muscle rupture leading to severe mitral regurgitation, managed with emergency surgical intervention and extracorporeal membrane oxygenation. The pa-tient, with a history of Type I Bipolar Disorder under long-term lithium therapy and chronic Cannabis use, presented in critical condition with cardiogenic shock (Killip IV), acute pulmonary edema, and ST-segment elevation myocardial infarction in the in-fero-posterior territory. Coronary angiography revealed right coronary artery occlusion and involvement of an obtuse marginal branch. Emergency mitral valve replacement with a mechanical prosthesis and aortocoronary bypass were performed. Due to failure to wean from cardiopulmonary bypass, central veno-arterial ECMO was initiated. The postoperative course was complicated by hemodynamic instability and recurrent peri-cardial collections requiring repeated surgical interventions and conversion to periph-eral ECMO. Multiorgan dysfunction developed, including hepato-renal failure requiring hemofiltration, neurological injury, respiratory impairment, and neuropsychiatric complications. Despite these challenges, progressive recovery was achieved under in-tensive multidisciplinary management. This case emphasizes the importance of early surgical correction and tailored ECMO support in managing post-infarction mechanical complications.